Budesonide

Description

Budesonide, USP, the active component of budesonide inhalation suspension, is a corticosteroid designated chemically as (RS)-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. It is provided as a mixture of two epimers (22R and 22S). Budesonide, USP appears as a white to off-white, tasteless, odorless powder that is practically insoluble in water and in heptane, sparingly soluble in ethanol, and freely soluble in chloroform. The partition coefficient between octanol and water at pH 7.4 is 1.6 x 10^3.

Budesonide inhalation suspension is a sterile suspension intended for inhalation via jet nebulizer. It contains the active ingredient budesonide, USP (micronized), along with inactive ingredients including citric acid monohydrate, disodium edetate, polysorbate 80, sodium chloride, tri-sodium citrate dihydrate, and water for injection. The product is available in two dose strengths in single-dose vials: 0.25 mg and 0.5 mg per 2 mL vial.

Uses and Indications

Budesonide inhalation suspension is indicated for the maintenance treatment of asthma and as prophylactic therapy in pediatric patients aged 12 months to 8 years.

This drug is not indicated for the relief of acute bronchospasm. There are no teratogenic or nonteratogenic effects associated with its use.

Dosage and Administration

The initial dosing regimen should commence with the lowest recommended dose tailored to the specific treatment modality. For bronchodilators administered alone, the starting dose is 0.5 mg once daily or 0.25 mg twice daily. In the case of inhaled corticosteroids, the recommended starting dose is 0.5 mg once daily or 0.25 mg twice daily, with the option to increase to a maximum of 0.5 mg twice daily if necessary. For oral corticosteroids, the initial dose is 0.5 mg twice daily.

In symptomatic children who do not respond adequately to non-steroidal therapy, a starting dose of 0.25 mg once daily may be considered. Should once-daily treatment fail to achieve sufficient control of symptoms, the total daily dose may be increased and/or administered as a divided dose. Once asthma stability is attained, it is advisable to titrate the dose downwards to the lowest effective level.

This medication is intended for inhalation use exclusively via compressed air-driven jet nebulizers; it is not suitable for use with ultrasonic devices and is not for injection.

Contraindications

Use of budesonide inhalation suspension is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma that require intensive measures. Additionally, it is contraindicated in patients with a known hypersensitivity to any of the ingredients in the formulation.

Warnings and Precautions

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur in patients using budesonide inhalation suspension. Healthcare professionals should monitor patients periodically for signs of adverse effects on the oral cavity and advise them to rinse their mouth following inhalation to mitigate this risk.

Budesonide inhalation suspension is not indicated for the relief of acute bronchospasm. Therefore, it should not be used in the management of acute asthma episodes or the deterioration of disease.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. If any of these reactions occur, the use of budesonide inhalation suspension should be discontinued immediately.

Immunosuppression is a potential concern, particularly in patients with existing infections such as tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is advised when prescribing budesonide inhalation suspension to these patients, as they may experience a more serious or even fatal course of chickenpox or measles.

When transferring patients from systemic corticosteroid therapy to budesonide inhalation suspension, there is a risk of impaired adrenal function. It is essential to taper patients slowly from oral steroids to minimize this risk.

Hypercorticism and adrenal suppression may occur, particularly with very high dosages or in susceptible individuals. Should these changes arise, the dosage of budesonide inhalation suspension should be reduced gradually.

Long-term administration of budesonide inhalation suspension may lead to a reduction in bone mineral density. Therefore, it is crucial to monitor patients who have major risk factors for decreased bone mineral content.

In pediatric patients, growth should be closely monitored during treatment with budesonide inhalation suspension to ensure that any potential effects on growth are identified and managed appropriately.

Patients should be monitored for the development of glaucoma and cataracts, as these conditions may be exacerbated by the use of budesonide inhalation suspension.

In the event of paradoxical bronchospasm, the use of budesonide inhalation suspension should be discontinued, and alternative therapy should be initiated.

Healthcare professionals should remain vigilant for eosinophilic conditions, including Churg-Strauss syndrome, in patients receiving budesonide inhalation suspension.

To ensure patient safety, it is recommended to conduct regular laboratory tests, including monitoring for decreased bone mineral content in at-risk patients, tracking growth in pediatric patients, and maintaining close observation for glaucoma and cataracts.

Side Effects

Most common adverse reactions observed in patients include respiratory infections, rhinitis, coughing, otitis media, viral infections, moniliasis, gastroenteritis, vomiting, diarrhea, abdominal pain, ear infections, epistaxis, conjunctivitis, and rash.

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur. It is recommended that patients be monitored periodically for signs of adverse effects on the oral cavity, and they should be advised to rinse their mouths following inhalation.

Patients should be cautioned against using budesonide inhalation suspension for the relief of acute bronchospasm, as it may lead to deterioration of disease and acute asthma episodes. Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. If such reactions occur, discontinuation of budesonide inhalation suspension is advised.

Immunosuppression may occur, leading to a potential worsening of infections, including existing tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is warranted when using this medication in patients with these infections. Additionally, susceptible patients may experience a more serious or even fatal course of chickenpox or measles.

When transferring patients from systemic corticosteroid therapy to budesonide inhalation suspension, there is a risk of impaired adrenal function. It is essential to taper patients slowly from systemic corticosteroids to mitigate this risk. Hypercorticism and adrenal suppression may occur, particularly with very high dosages or at regular dosages in susceptible individuals; if such changes are observed, a gradual reduction of budesonide inhalation suspension is recommended.

Long-term administration of budesonide inhalation suspension may lead to a reduction in bone mineral density, necessitating monitoring in patients with major risk factors for decreased bone mineral content. Furthermore, the growth of pediatric patients should be closely monitored, as a dose-dependent effect on growth has been noted, with reductions in growth velocity associated with inhaled corticosteroids. The long-term implications of this reduction in growth velocity remain unknown.

Patients should also be monitored for glaucoma and cataracts, as close observation is warranted. In rare cases, paradoxical bronchospasm may occur; if this happens, budesonide inhalation suspension should be discontinued, and alternative therapy should be instituted. Additionally, healthcare providers should remain vigilant for eosinophilic conditions, including Churg-Strauss syndrome.

In clinical trials, pneumonia was observed more frequently in pediatric patients treated with budesonide inhalation suspension compared to those treated with placebo.

Drug Interactions

The concomitant use of strong Cytochrome P450 3A4 inhibitors, such as ritonavir, should be approached with caution. This combination may lead to an increase in systemic corticosteroid effects, which could enhance the risk of adverse reactions associated with corticosteroid therapy.

Monitoring for signs of increased corticosteroid effects is recommended, and dosage adjustments may be necessary based on the clinical response and tolerance of the patient.

Packaging & NDC

The table below lists all NDC Code configurations of Budesonide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness of budesonide inhalation suspension in pediatric patients aged six months to 12 months have been evaluated but not established. In children aged 12 months to 8 years, safety and effectiveness have been established. A 12-week study involving 141 pediatric patients aged 6 to 12 months with mild to moderate asthma or recurrent/persistent wheezing assessed adrenal-axis function using an ACTH stimulation test. The results indicated no significant adrenal suppression in patients receiving budesonide inhalation suspension compared to placebo.

However, pneumonia was observed more frequently in patients treated with budesonide inhalation suspension than in those receiving placebo. The study also noted a dose-dependent effect on growth; infants in the placebo group experienced an average growth of 3.7 cm over 12 weeks, while those receiving budesonide inhalation suspension showed average growths of 3.5 cm and 3.1 cm for the 0.5 mg and 1 mg doses, respectively. These findings suggest that the use of budesonide inhalation suspension in infants aged 6 to 12 months may lead to systemic effects, consistent with growth suppression observed in other studies involving inhaled corticosteroids.

Controlled clinical studies indicate that inhaled corticosteroids can reduce growth velocity in pediatric patients, with an average reduction of approximately one centimeter per year. The long-term implications of this reduction on final adult height remain unknown, and the potential for "catch-up" growth following discontinuation of treatment has not been adequately studied. In a separate study of asthmatic children aged 5 to 12 years, those treated with budesonide via a dry powder inhaler experienced a 1.1 cm reduction in growth compared to those receiving placebo after one year.

Routine monitoring of growth in pediatric patients receiving inhaled corticosteroids, including budesonide inhalation suspension, is recommended, utilizing methods such as stadiometry. To minimize systemic effects, it is advised that each patient be titrated to their lowest effective dose.

Geriatric Use

In clinical trials involving budesonide inhalation suspension, 30% of the 215 patients studied were aged 65 years or older, with 10% being 75 years of age or older. The data indicate that there are no overall differences in safety profiles between elderly patients and their younger counterparts. Furthermore, additional clinical and medical surveillance has not revealed any significant differences in responses to treatment between geriatric patients and younger individuals.

Given the lack of observed differences in safety and efficacy, no specific dosage adjustments are recommended for elderly patients. However, healthcare providers should remain vigilant in monitoring this population for any potential adverse effects, as individual responses may vary. It is essential to consider the overall health status and comorbidities of geriatric patients when prescribing budesonide inhalation suspension.

Pregnancy

There are no adequate well-controlled studies of budesonide inhalation suspension in pregnant women. However, published studies have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy. The estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

In animal reproduction studies, budesonide has been associated with structural abnormalities, embryocidal effects, and reduced fetal weights in rats and rabbits at doses less than the maximum recommended human daily inhalation dose (MRHDID). Specifically, fetal loss, decreased fetal weight, and skeletal abnormalities were observed in pregnant rabbits at doses 0.5 times the MRHDID, while similar adverse effects were noted in pregnant rats at doses approximately 5 times the MRHDID. No structural abnormalities or embryocidal effects were seen in pregnant rats at doses approximately 2 times the MRHDID. Additionally, budesonide affected growth and development of offspring, resulting in reduced survival and decreased mean body weights at doses less than 0.2 times the MRHDID.

In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes, including preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Therefore, pregnant women with asthma should be closely monitored, and medication should be adjusted as necessary to maintain optimal asthma control.

Studies indicate no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy. The rate of recorded congenital malformations among infants whose mothers were exposed to inhaled budesonide during early pregnancy was similar to the general population rate (3.8% vs. 3.5%). Furthermore, the number of infants born with orofacial clefts after exposure to inhaled budesonide was comparable to the expected number in the normal population (4 children vs. 3.3).

There are no well-controlled human studies that have investigated the effects of budesonide inhalation suspension during labor and delivery. Given the potential risks associated with poorly controlled asthma, healthcare professionals should weigh the benefits of asthma control against the potential risks of budesonide use during pregnancy.

Lactation

Budesonide inhalation suspension is present in human milk; however, there are no available data on its effects on the breastfed child or on milk production. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for budesonide inhalation suspension and any potential adverse effects on the breastfed infant from the medication or from the underlying maternal condition.

Human data indicate that when budesonide is delivered via dry powder inhaler, the total daily oral dose of budesonide available in breast milk to the infant is approximately 0.3% to 1% of the dose inhaled by the mother.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Acute toxic effects following an overdose of budesonide inhalation suspension are considered to be low. However, it is important for healthcare professionals to be aware of the potential systemic effects that may arise from the excessive use of inhaled corticosteroids over extended periods.

Potential Symptoms

In cases of prolonged excessive dosing, patients may experience systemic corticosteroid effects, which can include hypercorticism and growth suppression. These symptoms are indicative of the body's response to elevated corticosteroid levels and warrant careful monitoring.

Recommended Actions

In the event of suspected overdose, it is advisable to assess the patient's clinical status and consider the duration and amount of budesonide inhalation suspension used. While acute toxicity is unlikely, healthcare providers should remain vigilant for signs of systemic corticosteroid effects. If such effects are observed, appropriate management strategies should be implemented, which may include dose adjustment or discontinuation of the medication, depending on the severity of the symptoms and the clinical judgment of the healthcare provider.

Overall, while the risk of acute toxicity is low, awareness and monitoring for potential systemic effects are essential in managing patients who may have overdosed on budesonide inhalation suspension.

Nonclinical Toxicology

In a two-year study conducted in Sprague-Dawley rats, budesonide was associated with a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg, which corresponds to approximately 0.5 and 0.1 times the maximum recommended human daily intake dose (MRHDID) in adults and children aged 12 months to 8 years, respectively, on a mcg/m² basis. No tumorigenicity was observed in male rats at oral doses up to 25 mcg/kg (approximately 0.2 and 0.04 times the MRHDID) and in female rats at doses up to 50 mcg/kg.

In two additional two-year studies involving male Fischer and Sprague-Dawley rats, budesonide did not induce gliomas at an oral dose of 50 mcg/kg. However, a statistically significant increase in the incidence of hepatocellular tumors was noted in male Sprague-Dawley rats at the same dose. The concurrent reference corticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings in these studies.

A 91-week study in mice revealed no treatment-related carcinogenicity at oral doses up to 200 mcg/kg, which is approximately equivalent to and 0.1 times the MRHDID in adults and children aged 12 months to 8 years on a mcg/m² basis.

Budesonide was evaluated for mutagenicity and clastogenicity in six different test systems, including the Ames Salmonella/microsome plate test, mouse micronucleus test, mouse lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, and DNA repair analysis in rat hepatocyte culture. The results indicated that budesonide was neither mutagenic nor clastogenic.

Fertility and reproductive performance were unaffected in rats at subcutaneous doses up to 80 mcg/kg, which is approximately equivalent to the MRHDID in adults on a mcg/m² basis. However, a decrease in prenatal viability and viability of pups at birth and during lactation was observed at subcutaneous doses of 20 mcg/kg and above, approximately 0.2 times the MRHDID in adults on a mcg/m² basis. No such effects were noted at a dose of 5 mcg/kg, which corresponds to approximately 0.05 times the MRHDID in adults on a mcg/m² basis.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of budesonide inhalation suspension, reported voluntarily or through surveillance programs.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been documented. Additionally, cases of thrush (candida), a fungal infection affecting the mouth and throat, have been reported. There have been instances of worsening asthma or sudden asthma attacks following administration.

Allergic reactions have also been noted, characterized by skin rash, redness or swelling, severe itching, facial swelling, swelling of the mouth and tongue, difficulty breathing or swallowing, chest pain, and feelings of anxiety.

Further, immune system effects have been observed, leading to an increased risk of infections. Reports of adrenal insufficiency have included symptoms such as tiredness, weakness, nausea, vomiting, and low blood pressure.

Other noted effects include a decrease in bone mineral density, potential for slowed or delayed growth, and eye problems such as glaucoma and cataracts. Increased wheezing immediately after taking budesonide inhalation suspension has also been reported.

Patient Counseling

Patients should be advised that budesonide inhalation suspension must be administered using a jet nebulizer connected to a compressor that provides adequate airflow, utilizing either a mouthpiece or a suitable face mask. It is important to inform patients that ultrasonic nebulizers are not appropriate for the administration of budesonide inhalation suspension and should not be used.

Patients should be made aware of the potential for localized infections with Candida albicans in the mouth and pharynx. In the event that oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic antifungal therapy while continuing therapy with budesonide inhalation suspension. However, there may be instances where therapy with budesonide inhalation suspension needs to be temporarily interrupted under close medical supervision. Patients are advised to rinse their mouths after inhalation to help mitigate this risk.

It is crucial to inform patients that budesonide inhalation suspension is not intended to relieve acute asthma symptoms, and they should not use extra doses for this purpose. Acute symptoms should be managed with an inhaled, short-acting beta2-agonist, such as albuterol. Patients should be instructed to notify their healthcare professional immediately if they experience any of the following: a decrease in the effectiveness of inhaled, short-acting beta2-agonists; an increased need for inhalations of inhaled, short-acting beta2-agonists; or a significant decrease in lung function as outlined by their physician.

Patients should not discontinue therapy with budesonide inhalation suspension without consulting their healthcare provider, as symptoms may recur following discontinuation. Additionally, hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported with the use of budesonide inhalation suspension. Patients should be advised to discontinue the medication if such reactions occur.

For patients on immunosuppressant doses of corticosteroids, it is important to warn them to avoid exposure to chickenpox or measles. If exposure occurs, they should consult their physician without delay, especially if the child has not had chickenpox or has not been properly vaccinated. Patients should also be informed of the potential for worsening existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.

Patients should be made aware that budesonide inhalation suspension may lead to systemic corticosteroid effects, including hypercorticism and adrenal suppression. They should be informed that there have been reports of deaths due to adrenal insufficiency during and after transitioning from systemic corticosteroids. Therefore, patients should taper slowly from systemic corticosteroids when transitioning to budesonide inhalation suspension.

Patients at increased risk for decreased bone mineral density should be advised that the use of corticosteroids may further elevate this risk. Furthermore, it is important to inform patients that orally inhaled corticosteroids, including budesonide inhalation suspension, may reduce growth velocity in pediatric patients. Healthcare professionals should closely monitor the growth of children and adolescents receiving corticosteroids by any route.

Long-term use of inhaled corticosteroids may increase the risk of certain eye problems, such as cataracts or glaucoma; therefore, regular eye examinations should be considered. Patients should be advised to use budesonide inhalation suspension at regular intervals, either once or twice a day, as its effectiveness is contingent upon consistent use. Maximum benefit may not be realized for 4 to 6 weeks or longer after initiating treatment. If symptoms do not improve within this timeframe or if the condition worsens, patients should be instructed to contact their healthcare professional.

Storage and Handling

The product is supplied in vials that must be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to protect the vials from light to maintain product integrity.

Once a vial has been opened, it should be used promptly to ensure efficacy. Prior to use, the vial should be gently shaken using a circular motion. It is important to note that the product must not be frozen, as this may compromise its quality.

Additional Clinical Information

Patients using budesonide inhalation suspension should be advised to rinse their mouths after each inhalation to minimize potential side effects. It is crucial for patients to contact their physician immediately if they experience asthma episodes that do not respond to their usual bronchodilator doses during treatment.

Additionally, patients who have previously been maintained on 20 mg or more per day of prednisone (or its equivalent) may be at increased risk for adrenal insufficiency when transitioning from systemic corticosteroids to inhaled corticosteroids. Therefore, it is recommended that these patients carry a medical identification card indicating their need for supplementary systemic corticosteroids during times of stress or severe asthma attacks.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Budesonide as submitted by Cardinal Health 107, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)